High-resolution profile of neoantigen-specific TCR activation links moderate stimulation to increased resilience of engineered TCR-T cells.

ABSTRACT: Neoantigen-specific T cell receptors (neoTCRs) promise safe, personalized anti-tumor immunotherapy. However, detailed assessment of neoTCR-characteristics affecting therapeutic efficacy is mostly missing. Previously, we identified diverse neoTCRs restricted to different neoantigens in a melanoma patient. In this work, we now combine single-cell TCR-sequencing and RNA-sequencing after neoantigen-specific restimulation of peripheral blood-derived CD8⁺ T cells of this patient. We detect neoTCRs with specificity for the previously detected neoantigens and perform fine-characterization of neoTCR-transgenic (tg) T cells in vitro and in vivo. We describe a heterogeneous spectrum of TCR-intrinsic activation patterns in response to a shared neoepitope ranging from previously detected mor

SUBMITTER: Fuchsl F 

PROVIDER: S-EPMC11615276 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature